The planned studies in this request continue to be directed toward the clarification of the interrelationships between hormones, tissues, and circulating and stored metabolites in man in various nutritional and disease states. Inquiries into the mechanisms by which starved man is able to defend his limited stores of body protein will continue. Hormonal mechanisms involving insulin and triiodothyronine will receive close attention with respect to their capacity to modulate muscle protein degradation and synthesis in both fed and fasted subjects. The impact of substrate concentrations on muscle metabolism in both nutritional states will be considered. Attention will be focused on the role played by physical activity in determining muscle protein content. In addition to a series of human forearm studies, which constitute a direct continuation of our previous work, we are developing an animal model, the chronic catheterized dog, and a cultured cell model, the L6 myoblasts. The integration of observations from these different experimental systems should lead to a better understanding of normal physiology and offer insight into disordered physiology in diseases such as trauma, diabetes, and uremia. Ultimately, we expect this work to lead to improved management of metabolic disturbances in human disease.